HIV, also known as LAV or HTLV III, is the causative agent of Acquired Immuno-Deficiency Syndrome (AIDS) (Barre-Sinoussi et al. 1983 Science 220, 868; Gallo et al. 1984 Science 224, 500; Levy et al. 1984 Science 225, 840; Clavel et al. 1986 Nature 324 691). At present there is no cure for AIDS nor is there a vaccine available. The genetic organization and the entire nucleotide sequence of HIV is know (Ratner et al. 1985 Nature 313, 277; Wain-Hobson et al. 1985 Cell 40, 9; Muesing et al. 1985 Nature 313 450; Sandoz-Pescador et al. 1985 Science 227 484). HIV is a lentivirus-like retrovirus with gag, pol and env genes like other retroviruses but it also contains additional coding sequences, sor, tat. art/trs and 3' orf that are involved in various aspects of virus replication and expression (Sodroski et al. 1985 Science 227, 171; Sodroski et al. 1986 Nature 319, 555; Sodroski et al. 1986 Nature 321, 412; Feinberg et al. 1986 Cell 46, 807) although the functions of sor and 3'orf are unclear.
Three general approaches can be used to produce an HIV vaccine. First, large amounts of HIV can be grown and inactivated to provide antigen. Second, recombinant DNA techniques can be used to produce HIV antigens either as simple monomeric proteins (e.g. Putney et al. (1986) Science 234 1392; Laskey et al. 1986 Science 233 209) or as vaccinia virus hybrids, although it is not clear that general use of a live vaccinia based system will ever be considered safe (e.g. Chakrabarti et al. 1986 Nature 320, 535; Zagury et al. 1987 Nature 326, 249). Third, synthetic peptides might be useful (Kennedy et al. 1986 Science 231 1556; Chanh et al. EMBO J. 5 3065).
Most of the work to date on producing HIV antigens has focussed on the production of the two surface glycoproteins encoded by the env gene, gp120 and gp41 (Putney et al. op. cit.; Laskey et al. op. cit.; Certa et al. 1986 EMBO J. 5 3051) although there has been some work on other antigens, e.g. tat III (Aldovini et al. 1986 PNAS 83 6672), sor (Kan et al. 1986 Science 231 1553), pol (Veronese et al. 1986 Science 233 1289; Kramer et al. 1986 Science 231 1580). The production of HIV antigens for vaccines or diagnostics and research material by recombinant DNA technology has three key advantages over production based on propagation of the virus. First, it is safe. Second, high yields can be achieved (Putney et al. op. cit.) by using high efficiency expression systems. Third, it is versatile in that antigenic domains that might normally be concealed may be exposed, a vaccine antigen could be marked with some other antigen to distinguish vaccination from infection or composite antigens might be produced.
A substantial disadvantage of most antigens produced by recombinant DNA techniques for vaccines is that they are usually made as simple monomeric proteins. This is not the ideal configuration for an immunising antigen as it does not readily permit the cross-linking of the components of the immune system that is required for maximum stimulation of humoral and cellular immunity. An ideal immunogen is a polymer of multiple antigenic determinants assembled into a high molecular weight carrier. A good immunogen should also have the maximum number epitopes exposed. This is best achieved by presenting multiple copies of the antigen on the surface of a particle. For this reason it would be desirable to develop polyvalent, particulate carrier systems for immunising antigens.